Do we have enough evidence on the clinical need and benefit of · – PQ Bypass (minor) – AneuMed (minor) • Officer, Director, Board Member or other Fiduciary Role –VIVA Physicians

Do we have enough evidence on the clinical need and benefit of

venous interventions?

Michael Dake, MD

Stanford University School of Medicine

Stanford, CA, USA

Michael Dake, MD

• Research/Research Grants, Clinical Trial Support– W. L. Gore (major)– Cook Medical (major)

• Consulting Fees/Honoraria– W. L. Gore– Cook Medical – Abbott Vascular (minor)– Medtronic (minor)– Cardinal Health (minor)

• Equity Interests/Stock Option– TriVascular (minor)– Intact Vascular (minor)– Arsenal (minor)– 480 Medical (minor)– PQ Bypass (minor)– AneuMed (minor)

• Officer, Director, Board Member or other Fiduciary Role– VIVA Physicians Group

• Speaker’s Bureau– None

Within the past 12 months, the presenter or

their spouse/partner have had a financial interest/arrangement

or affiliation with the organization listed below.

• Deep vein thrombosis and PE impose substantial economic burdens

• In a 2014 US study, 5442 DVT and 6119 PE health insurance claims and associated short- and long-term disability claims were analyzed to determine economic impact

Venous Thrombosis Complications: Societal Perspective

DVT, deep vein thrombosis; PE, pulmonary embolism

Page RL, et al. J Occup Environ Med. 2014;56(9):979-85.

Substantial Productivity Loss for Employees with DVT or PE

Days Lost Productivity Loss

Short-Term Claims

Long-Term Claims

Short-Term Claims

Long-TermClaims

DVT 57 days 440 days $7,414 $58,181

PE 56 days 364 days $7,605 $48,751

Note: Productivity loss and missed days associated with short-term and long term disability claims were

calculated per each disability incident

• 20-50% of patients with DVT develop PTS1,2

• Symptoms and signs:3

– Leg pain or heaviness

– Leg edema

– Redness or dusky cyanosis

– Telangiectasia

– New varicose veins

– Stasis hyperpigmentation

– Skin thickening

– Leg ulcers

Venous Thrombosis Complications: Post-Thrombotic Syndrome (PTS)

1. Kahn SR, et al. Ann Intern Med. 2008 149(10):698-707.

2. Prandoni P, et al. Ann Intern Med. 1996;125(1):1-7.

3. Kahn SR, et al. J Thromb Thrombolysis. 2016;41(1):144-53

An estimated 761,697 non-fatal VTE events and 399,808 associated complications occurred across the six European countries in 2004

Cohen AT, et al; VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. Thromb Haemost. 2007 Oct;98(4):756-64.

Venous Thromboembolism (VTE): Annual European Estimate

Year 2004 data from France, Germany, Italy, Spain, Sweden, and the UK

Non-fatal VTE event Chronic Complications

Deep-VeinThrombosis

Pulmonary Embolism

Post-Thrombotic Syndrome

Pulmonary Hypertension

Total Number of Community &

Hospital Acquired Events

465,715 295,982 395,673 4,135

AngioJetTM

Thrombectomy System (Boston

Scientific)IndigoTM

(Penumbra)EKOSTM

(BTG)AspirexTM

(Straub)RotarexTM

(Straub)

CatheterDirected lytic

(e.g. Angiodynamics

Uni*FuseTM)

Regulatory Approval

Mechanical Thrombectomy

CE Mark/FDAApproved to break apart and remove

thrombus

FDA -- CE Mark CE Mark --

Pharmaco-mechanical

CE Mark/FDAApproved for both

thrombectomy and infusion of

fluids (via Power Pulse™)

--FDA

Fluid infusion w/ ultrasound

-- --FDA

Pharmacologiconly

Aspiration mechanism

High speed jets inside catheter

paired with ULTRA console (-600 mm

Hg)

External vacuum pump (-

29mm Hg) None

Rotating helix produces a negative pressure and acts as the conveyor screw for the material transported

into the collecting bag

None

Maximum aspiration capacity (maximum blood loss)

60 mL/min480 mL/min

(CAT 8)--

6F: 45 mL/min8F: 75 mL/min

10F: 130 mL/min--

Indications

• Veins• Arteries• Arterio-venous

fistula grafts

Generalvasculature

Fresh, soft emboli and

thrombi

• Venous• Arterial• Pulmonary

emboli

Acute occlusions:• Veins• Arteries• Dialysis

access

• Veins• Arteries• Dialysis

access• In-stent

restenosis

Peripheral vasculature

Sources: Indigo Product Brochure; EKOS EkoSonic Instructions for Use; www.angiodynamics.com/products/UniFuse; http://www.straubmedical.com/documentation.html

Thrombectomy/Thrombolysis Devices

CAUTION: The law restricts these devices to sale by or on the order of a physician.

PEARL* Venous Registry†CaVenT‡

CDT Standard

# of Patients 329 287 90 99

# of Sites 32 63 20

Primary Treatment AngioJet Thrombectomy

With or Without PMT CDT CDT LMWH

Prior DVT 40% 31% 10% 9%

Stent Placement 35% 33% 17% NA

Primary access Popliteal Popliteal Popliteal NA

Male 57% 48% 64% 62%

Age (mean) 52.2 yrs 47.5 yrs 53.3 yrs 50.0 yrs

Treatment Location Iliofemoral – femoral pop Iliofemoral – femoral pop CFV or iliofemoral

Limbs Involved Left=62%; Right=38%

Left=61%; Right=39%

Left=60%; Right=40% Left=62%; Right=38%

CDT, catheter-directed thrombolysis; CFV, common femoral vein;

LMWH, low molecular weight heparin; PMT, pharmacomechanical thrombolysis

Results from different clinical investigations are not directly comparable.

Information provided for educational purposes only

*Garcia,MJ, et al. J Vasc Interv Radiol 2015; 26:777-785†Mewissen MW, Seabrook GR. Radiology 1999:211:39-49 ‡Enden , Haig Y. Lancet 2012:379:31-38

Study ComparisonTreatment of Lower Extremity DVT

Patient Characteristics


PEARL* Venous Registry†

CaVenT‡

CDT Standard

Onset of DVT

Symptoms

Acute 67% (≤14 days) 66% (≤10 Days ) 100% ≤21 days

Chronic 33% (>14 days) 16% (>10 Days ) NA

Acute & Chronic

NA 19% NA

Primary Lytic TPA Urokinase TPA NA

CDT Drip Times (mean) 17 hrs 48 hrs 57.6 hrs (2.4 days) NA

Procedure Times

CDT (N=29)

40.9 hrs NA NA NA

CDT+PPS/RL (N=172)

22.0 hrs NA NA NA

PPS/RL (N=115) 2.0 hrs NA NA NA

Bleeding Complications4.5% (major & minor

combined)11% (major); 16% (minor)

22% (major & minor combined)

0%

CDT, catheter-directed thrombolysis; PMT, pharmacomechanical thrombolysis;

PPS, power-pulse spray; RL, rheolytic; TPA, tissue plasminogen activator

Treatment Characteristics




PEARL*Venous

Registry†

CaVenT‡

CDT Standard

% Thrombus Removal

Overall 96% 83% 89% NA

CDT (N=28) 93% NA NA

CDT+PPS/RL (N=167) 97% NA NA

PPS/RL (N=113) 95% NA NA

Acute 97% 86% 89%

Chronic 95% 68% NA

Primary Patency NA6 Month = 65%

12 Month = 60%6 Month = 65.9% 6 Month = 47.4%

Freedom from Rethrombosis6 Month= 87%

12 Month= 83%NA NA NA


CDT, catheter-directed thrombolysis; PPS, power-pulse spray; RL, rheolytic




Treatment Effectiveness

Current DVT Treatment GuidelinesSummary

Meissner MH, et al. Early thrombus removal strategies for acute deep venous thrombosis: clinical practice guidelines of the Society for Vascular Surgery

and the American Venous Forum. J Vasc Surg. 2012;55(5):1449-62.

Nicolaides, A. N. et al. Prevention and Treatment of Venous Thromboembolism. International Union of Angiology (IUA). Volume 32, No 2. CDER Trust,

London, UK. April 2013.

Vedantham S, et al; Society of Interventional Radiology and Cardiovascular and Interventional Radiological Society of Europe Standards of Practice

Committees. Quality improvement guidelines for the treatment of lower-extremity deep vein thrombosis with use of endovascular thrombus removal. J

Vasc Interv Radiol. 2014;25(9):1317-25.

• Current guidelines generally recommend anticoagulation therapy and compression stockings as first line of treatment to prevent recurrent venous thromboembolism and reduce swelling

• Endovascular interventions (CDT and PMT) are currently considered for select patients who would benefit from early thrombus removal, especially those with acute iliofemoral DVT

Summary of the GuidelinesEndovascular Thrombus Removal

AVF, American Venous Forum; CDT, catheter-directed thrombolysis; IUA, International Union of Angiology; PMT, pharmacomechanical thrombectomy;

SIR, Society of Interventional Radiology; SVS, Society for Vascular Surgery

SVS/AVF- Meissner MH, et al. J Vasc Surg. 2012;55(5):1449-62.

IUA- Nicolaides AN, et al. International Union of Angiology (IUA). Volume 32, No 2. CDER Trust, London, UK. April 2013.

SIR- Vedantham S, et al. J Vasc Interv Radiol. 2014;25(9):1317-25.

Thrombus Removal Method Indications

PMT preferred • Acute iliofemoral DVT (IUA, SVS/AVF)

PMT/CDT- no preference

• Symptomatic iliofemoral DVT, select patients with femoral DVT (SIR)

• Limb-threatening venous ischemia due to iliofemoral deep venous thrombosis (SVS/AVF, SIR)

Percutaneous mechanical thrombectomy alone

• Not recommended for acute DVT (IUA)

Surgical thrombectomy • Iliofemoral DVT, if thrombolytic therapy is contraindicated

(SVS/AVF)

Do we have enough evidence on the clinical need and benefit of

venous interventions?

Michael Dake, MD

Stanford University School of Medicine

Stanford, CA, USA

Documents

Do we have enough evidence on the clinical need and benefit of · – PQ Bypass (minor) – AneuMed (minor) • Officer, Director, Board Member or other Fiduciary Role –VIVA Physicians